Is ITGA7 p.Phe281= (c.843T>C) pathogenic?

ITGA7 p.Phe281= (c.843T>C) is classified Likely benign in ITGA7 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-22). Ultra-rare (popmax 0.0134%, eas); Associated with congenital muscular dystrophy due to integrin alpha-7 deficiency.

What condition is associated with ITGA7 p.Phe281= (c.843T>C)?

ITGA7 p.Phe281= (c.843T>C) is associated with congenital muscular dystrophy due to integrin alpha-7 deficiency (ClinVar).

How common is ITGA7 p.Phe281= (c.843T>C) in the general population?

ITGA7 p.Phe281= (c.843T>C) is ultra-rare (popmax 0.0134%, eas) (gnomAD).

ITGA7 p.Phe281=

Q: How is Congenital muscular dystrophy with integrin alpha-7 deficiency inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

c.843T>C · rs573236644 · VCV2897739

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0134%, eas)

Conditions

congenital muscular dystrophy due to integrin alpha-7 deficiency

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.7	GERP -0.32, phastCons 1
Overall
CADD	11.7	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0134% East Asian · 6/44,886 alleles

Filtering AF 0.00579% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00394%

Overall 0.000372% 6/1,613,990 alleles · ultra-rare exomes 4/1,461,700 · genomes 2/152,290 · joint denominator

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: ITGA7
Protein: p.Phe281=
Coding: c.843T>C
MANE Select: NM_002206
dbSNP: rs573236644
Type: single nucleotide variant
Location: chr12:55698865 (GRCh38)
Gene constraint: LOEUF 0.738 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.14

Full ITGA7 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

congenital muscular dystrophy due to integrin alpha-7 deficiency — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Congenital muscular dystrophy with integrin alpha-7 deficiency (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal
Prevalence: <1 / 1 000 000 (Europe)

Similar variants

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ITGA7 p.Arg569Ter Pathogenic/Likely pathogenic ★★ same condition
ITGA7 p.Arg604Ter Pathogenic/Likely pathogenic ★★ same condition
ITGA7 p.Arg798Ter Pathogenic/Likely pathogenic ★★ same condition
ITGA7 p.Gln76Ter Pathogenic/Likely pathogenic ★★ same condition
ITGA7 p.Gln83Ter Pathogenic/Likely pathogenic ★★ same condition

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/itga7-p-phe281 (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown